Study on the regulation of lipid signaling in pancreatic β-cells and the pathogenesis of diabetes mellitus

甘油二酯激酶（DGK）将甘油二酯（DAG）磷酸化为磷脂酸，并严格调节这些脂质分子的细胞内水平。在小鼠胰岛和β细胞系MIN 6中检测到I型DGK（DGKα和γ）的表达。一种特异性的I型DGK抑制剂抑制MIN 6细胞的胰岛素分泌和[Ca ~（2+）]i。此外，DGKα和γ的siRNA双敲低导致胰岛素分泌显著减少。膜可渗透的DAG类似物也抑制MIN 6细胞中[Ca 2 +] i升高。这些结果表明，DGKα和γ存在于β细胞中，并且由于这些DGK同种型的功能减退而导致的β细胞中DAG积累导致[Ca 2 +]i降低，从而减少胰岛素分泌。I型DGK可能成为糖尿病治疗的新靶点。

Diacylglycerol kinases (DGK) phosphorylate diacylglycerol (DAG) to phosphatidic acid and strictly regulate the intracellular level of these lipid molecules. The expression of type I DGK (DGKαand γ) was detected in mouse pancreatic islets and the β-cell line MIN6. A specific type I DGK inhibitor inhibited insulin secretions and Ca2+concentration ([Ca2+]i) in MIN6 cells. Moreover, DGKαand γdoubleknockdown by siRNA led to significant decreases in insulin secretions. A membrane permeable DAG analog also inhibited [Ca2+]ielevations in MIN6 cells. These results suggest that DGKαand γare present in β-cells, and that DAG accumulation in β-cells resulting from hypofunction of these DGK isoforms leads to a decrease in [Ca2+]i,thereby reducing insulin secretion. Type I DGK could be a novel therapeutic target for diabetes mellitus.